Excess adiposity, in its extreme form obesity, is generally regarded as a disorder of energy regulation. This disorder is increasingly prevalent in industrialized nations because of the abundance of food and the reduced activity levels that accompany the movement of populations from rural to urban settings. Obesity is loosely defined as an excess of body fat over that needed to maintain health.
Obesity is associated with increased morbidity and mortality. Detrimental effects of obesity on health, include an increased risk of cardiovascular disease and the associated conditions of hypertension, diabetes, and hyperlipidemia. Millions of people are clinically obese (i.e., a Body Mass Index value above the 851 h percentile), and, in view of the deleterious effects of obesity on health, would benefit from treatment. Additionally, many people, although not clinically obese, can improve their health and well-being by losing weight.
The pathogenesis of obesity is multifactorial and includes the control of feeding behavior, mechanisms of fat storage, the components of energy intake and expenditure, and genetic and psychological influences. Likewise, the treatment of obesity is generally multifactorial. Unfortunately, the mechanisms of fat storage and genetic influences are not, generally speaking, amenable to treatment. Moreover, the control of feeding behavior and psychological influences require protracted treatment. In addition, although the components of energy intake and expenditure are treatable, many obese individuals are resistant to or incapable of engaging in activities which significantly increase their energy expenditure. Therefore, controlling energy intake is an attractive approach for the treatment of obesity.
In addition to the voluntary reduction of food consumption, a variety of anorectic agents have been used to reduce energy intake. However, pharmacologic doses of anorectic agents such as caffeine, fenfluramine hydrochloride and fluoxetine are not without deleterious side effects. For example, caffeine has been associated with nervousness and irritability, fenfluramine hydrochloride has been associated with drowsiness, diarrhea and dry mouth, and fluoxetine has been associated with anxiety, nervousness and insomnia. While some commonly prescribed drugs (e.g., erythromycin) have an anorectic effect, this occurs in a very small percentage of patients (e.g., fewer than 3%). Moreover, this effect is associated with a general adverse reaction of the gastrointestinal system (i.e., including nausea, vomiting, abdominal pain, and diarrhea). In light of the more than thirty-four million obese adults in the United States alone, a significant need for an anorectic agent with widespread applicability and a low incidence of adverse reactions is clearly indicated.